Synthesis and characterisation of dipyrromethene Cu(II) complexes: A preliminary DNA intercalation study

Abstract

Copper complexes of the bilirubin bile pigment have been shown to affect DNA. It was suggested that the copper ions within these metal-bilirubin therapeutics bind to bilirubin through the two dipyrromethene moieties, thus highlighting the potential therapeutic impact of these dipyrromethene moieties. Here, we report the synthesis and characterization of two bilirubin biomimetic copper complexes, CuL1 and CuL2, featuring tetrahedral dipyrromethene moieties. DNA binding studies reveal significant affinities for both complexes, with CuL1 displaying a log Ka of 4.70 ± 0.02, with a corresponding Gibbs free energy change (ΔG) of –26.8 kJ/mol at 25 °C, indicating a moderate-to-high DNA affinity. CuL2 showed a slightly higher affinity with log Ka of 4.88 ± 0.02, with a corresponding ΔG of –27.4 kJ/mol at 25 °C. These experimental findings aligned closely with computational docking G-scores, which yielded –32.9 kJ/mol for CuL1 and –34.8 kJ/mol for CuL2, respectively. Viscosity, gel electrophoresis, and absorption studies support an intercalative binding mechanism, which was further confirmed by computational docking and molecular dynamics simulations. These findings suggest that copper dipyrromethene complexes may exert therapeutic effects through DNA interaction, warranting further investigation involving in vitro cell cultures for drug development potential.